This invention relates to a liquid pharmaceutical preparation for oral delivery and to the preparation and use thereof. This invention further relates to liquid pharmaceutical preparations for oral delivery to children.
In many cases, it is desirable and/or necessary to deliver a pharmaceutical in liquid form. In general, in using such liquid pharmaceutical preparations, the pharmacist initially prepares a suspension of the pharmaceutically active material in a liquid carrier, and the suspension is placed into an appropriate container. At the time of use, the person using the preparation dispenses the liquid from the container into a spoon or dropper, which xe2x80x9cmeasuresxe2x80x9d the amount of the liquid suspension for oral delivery of the suspension in the proper dosage. For example, in the case of antibiotics for oral delivery as a liquid, the antibiotic is prepared as a dry mix. When called upon to constitute and dispense such product, the pharmacist generally loosens the powder at the bottom of the container by lightly tapping it against the hard surface. However, if this is not done correctly, drug will remain as a cake at the bottom of the container, which will cause a sub-potent dose of drug to be administered to the patient. Once the drug is loosened in the container, the pharmacist proceeds to add the label designated amount to purified water. It is important that the pharmacist add the exact amount of purified water to the powder if the proper drug concentration per unit dose is to be achieved. Typically, purified water is needed to constitute current commercial dry pharmaceutical powders for oral suspension because of stability issues with tap water. In addition liquid suspension of a pharmaceutical may not be stable. This instability may occur over the typical 7-14 day shelf life of current constituted suspensions.
The thus prepared suspension contains a plurality of unit dosages, and, therefore, when being used, the person who is to take the pharmaceutical dispenses a specified amount of the liquid suspension from the container. In general, the container specifies that the unit dosage form that is to be used is a convenient measure such as 5 milliliters or one teaspoonful. However, teaspoons typically vary in volume, and to the extent that the volume of a teaspoon is inaccurate, the person dispensing or taking the liquid usually does not precisely dispense a teaspoonful.
As a result, there is a variation in the amount of drug that a patient receives that may result from the pharmacist preparing the liquid suspension or the patient dispensing an incorrect amount of the liquid suspension.
In accordance with an aspect of the present invention, there is provided a pharmaceutical composition, as well as a process for preparing a pharmaceutical composition for oral delivery in a liquid carrier that permits the formulation and dispensing of more accurate dosages of a pharmaceutically active agent or material for oral delivery in a liquid carrier.
In accordance with an embodiment of the invention, there is provided a solid unit dosage form, which at the time of use is added to a pharmaceutically acceptable liquid, such as water wherein the unit dosage form is comprised of a substrate and a particulate pharmaceutically active material deposited on such substrate with the pharmaceutically active material being present on the substrate in a pharmaceutically effective amount. The substrate is one that disintegrates rapidly in the liquid to form a solution or suspension suitable for oral delivery in the liquid. In this manner, at the time of use, the solid unit dosage form, is added to a liquid, and the pharmaceutically active material can be orally delivered in a pharmaceutically effective dosage without measuring the quantity of liquid carrier at the time of use. Thus, the solid unit dosage form contains the required amount of pharmaceutically active material, and when it is added to liquid, the substrate disintegrates rapidly, and the particulate pharmaceutically active material is dissolved or suspended in the liquid. The liquid may include a syrup or other sweetener in order to improve the palatability of the liquid and pharmaceutically active material. The entire amount of liquid is then swallowed and since the solid dosage form contains the required amount of pharmaceutically active material, there is no need to measure the quantity of liquid in order to prepare the proper dosage. The pharmaceutically active material may be comprised of one or more pharmaceutically active agents.
In a preferred embodiment, the solid unit dosage form is one in which the pharmaceutically active agent(s) or material(s) is deposited on the substrate as a layer separate and distinct from the substrate. In a particularly preferred embodiment, the pharmaceutically active agent(s) or material(s) is deposited as a separate and distinct layer on the substrate without being blended with non-pharmaceutically active material. Thus, the pharmaceutically active agent(s) or material(s), in the solid unit dosage form, is not blended with other materials.
In another embodiment, a small quantity of one or more taste modifiers may be deposited on the substrate with pharmaceutically active agent.
The substrate is preferably soluble in a pharmaceutically acceptable liquid such as water and, more preferably, rapidly dissolves therein. As representative examples of substrates that may be used in the present invention, there may be mentioned: gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinyl alcohol, polyethylene oxide, polyvinylpyrrolidone, sodium alginate, carboxymethylcellulose, and agar. It is to be understood, however, that the scope of the invention is not limited to such substrates.
Thus, in accordance with an aspect of the present invention, there is provided a pharmaceutical composition that is a solid unit dosage form that is comprised of a substrate rapidly soluble in a pharmaceutically acceptable liquid such as water and a particulate pharmaceutically active material deposited on the substrate as a separate and distinct layer, wherein the pharmaceutically active material is present in a desired unit dosage amount, whereby the unit dosage form can be added to liquid, at the time of use, for oral delivery of the pharmaceutically active material in a liquid carrier.
In accordance with another aspect, the pharmaceutical composition is one which is for administration to children patients; i.e., patients no older than twelve years, wherein the amount of pharmaceutically active material present in the solid unit dosage form is both a pharmaceutically effective unit dosage amount and an amount suitable for administration to children.
In accordance with another aspect, the pharmaceutical composition is one which is for administration to geriatric patients; i.e., patients older than seventy years, wherein the amount of pharmaceutically active material present in the solid unit dosage form is both a pharmaceutically effective unit dosage amount and an amount suitable for administration to geriatric patients.
The invention is particularly applicable to the delivery of antibiotic and/or anti-viral and/or anti-fungal and/or anti-infective agents; however, the scope of the invention is not limited thereto. In a particularly preferred embodiment, the invention is directed to delivery of an antibiotic to children, wherein the unit dosage form contains a pharmaceutically effective amount of the antibiotic that is suitable for administration to children.
In accordance with a preferred embodiment of the present invention, a solid unit dosage form, which is to be added to a pharmaceutically acceptable liquid, such as water, for oral delivery in accordance with the present invention is preferably prepared by a process wherein the active ingredient is directly deposited onto an appropriate substrate, preferably by electrostatic deposition. Thus, for example, the pharmaceutically active material is electrostatically deposited onto substrate, which preferably dissolves rapidly in a pharmaceutically acceptable liquid such as water. In a preferred embodiment, a cover sheet of material identical or similar to the substrate may be placed over the pharmaceutical reagent on the substrate and sealed to the substrate. In an alternative embodiment, if a cover sheet is not used, the substrate can be rolled into a final dosage form.
The drug or pharmaceutical deposited onto the substrate may be further processed to yield a finished dosage form of a given shape or size.
At the time of use, the solid unit dosage form is added to a liquid, such as water, and in view of the fact that the solid unit dosage form contains the required amount of pharmaceutically active material(s), the patient receives an accurate dosage provided that all of the liquid to which the material is added is consumed, and such accurate dosage is obtained without necessitating the measurement of a controlled amount of liquid for forming the liquid pharmaceutical preparation. In accordance with an embodiment of the invention, a plurality of solid unit dosage forms are placed in an appropriate package; for example, a container, blister pack, etc., along with instructions that at the time of use, the unit dosage form is to be added to a liquid, such as water, and the contents swallowed.
In accordance with a preferred embodiment of the present invention, the solid unit dosage forms of the present invention are included in a package that contains a plurality of such unit dosage forms, and each of the unit dosage forms does not vary from a predetermined amount by more than about 5%.
As hereinabove indicated, in accordance with a preferred embodiment, the solid unit dosage forms that are to be packaged for subsequent addition to a pharmaceutically acceptable liquid, such as water, for oral delivery are produced by an electrostatic deposition process wherein the pharmaceutically active ingredient, as a powder, is applied to a suitable substrate. A preferred embodiment for producing such unit dosage form is illustrated in the accompanying drawings wherein: